Diagnostic efficacy of ACA, aß2-GP1, hs-CRP, and Hcy for cerebral infarction and their relationship with the disease severity.

OBJECTIVE: To evaluate the diagnostic efficacy of anti-cardiolipin antibodies (ACA), anti-ß2-glycoprotein I antibodies (aß2-GP1), high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) in cerebral infarction and to explore their relationship with disease severity. METHODS: Medical records of 67 cerebral infarction patients admitted from May 2020 to January 2023 and 50 healthy individuals undergoing health checkups were retrospectively analyzed. The levels of ACA, aß2-GP1, hs-CRP, and Hcy were compared, their correlation with National Institutes of Health Stroke Scale (NIHSS) scores was assessed, and their diagnostic efficacy across different disease severities were evaluated. A joint predictive score formula, defined as -6.054712173 + aß2-GP1*1.906727231 + Hcy*0.576221974, which combines aß2-GP1 and Hcy levels, was developed to assess the likelihood of cerebral infarction in our study population. RESULTS: The levels of ACA, aß2-GP1, hs-CRP and Hcy, and joint predictive score were significantly higher in the patient group (all P < 0.001). ROC analysis yielded AUCs of 0.887 for ACA, 0.894 for aß2-GP1, 0.899 for hs-CRP, 0.880 for Hcy, and 0.954 for the joint predictive score. Delong's test showed no statistical difference in most indicators compared to the joint predictive score (P > 0.05), except aß2-GP1 (P < 0.05). Pearson's correlation analysis indicated that aß2-GP1, Hcy, and the joint predictive score were positively correlated of with NIHSS score (all P < 0.05), while ACA and hs-CRP were not (P > 0.05). Notable differences in aß2-GP1 and the joint predictive score were observed among varying severity levels (P < 0.01), with the joint predictive score showing superior diagnostic efficacy in distinguishing between mild and moderate/severe cases (P < 0.01). CONCLUSION: ACA, aß2-GP1, hs-CRP, and Hcy are effective biomarkers for diagnosing cerebral infarction, and are positively correlated with disease severity. The joint predictive score demonstrates enhanced accuracy in discerning degree of severity.

Comparative assessment of the diagnostic performances of particle-based multianalyte technology and commercial ELISA for antiphospholipid autoantibody testing.

BACKGROUND: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-ß2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. METHODS: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT's performance was evaluated against commercial ELISA in detecting aPL antibodies. RESULTS: At the manufacturer's suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88-90% specificity), IgA and IgM antibodies yielded 5.9-17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. CONCLUSIONS: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.

Clinical and Laboratory Diagnosis of Antiphospholipid Syndrome: A Review.

The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-ß2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-ß2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.

Beta-2 Glycoprotein I IgA Isotype: An Important Consideration in Secondary Hypertension.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults.

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-ß2-glycoprotein I (ß2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.

Diagnostic significance of combined anti-extractable nuclear antigens antibody, anti-cardiolipin antibody and anti-ß2-glycoprotein 1 in systemic lupus erythematosus patients.

Objective: This study aimed to investigate the diagnostic value of a combination of anti-extractable nuclear antigens (anti-ENA) antibodies, anti-cardiolipin antibodies (ACA), and anti-ß2-glycoprotein 1 (anti-ß2 GPI) antibodies in patients with systemic lupus erythematosus (SLE). Methods: A total of 646 SLE patients diagnosed in our hospital between January 2020 and April 2023 were randomly selected as study subjects, while 2075 non-SLE subjects during the same period were selected as the control group. The levels of anti-extractable nuclear antigen (ENA) antibody, ACA, and anti-ß2 GPI antibodies were measured, and their diagnostic value for SLE was analyzed using binary logistic regression and receiver operating characteristic (ROC) analysis. Results: The rates of positive anti-RNP, anti-Sm, anti-Sjögren's syndrome (SS-A), and anti-SS-B antibodies in the SLE patient group were significantly higher than those in the control group, with all differences being statistically significant (P < 0.01). The rates of positive ACA, as well as the levels of ACA IgA, ACA IgG, and ACA IgM, were significantly higher in the SLE patients group compared to the control group, with statistically differences (P < 0.05). Similarly, the rates of positive anti-ß2 GPI antibodies, anti-ß2 GPI antibody IgA, IgG, and IgM, were significantly higher in the SLE patient group compared to the control group, with all differences being statistically significant (P < 0.01). Gender, age, positive anti-JO1 antibodies, positive anti-RNP antibodies, positive anti-SS-A antibodies, positive ACA, high level ACA IgG and ACA IgM, positive anti-ß2 GPI antibodies, and high level of anti-ß2 GPI antibody IgA were identified as independent risk factors for the development of SLE (P < 0.05). The combined use of age, sex, anti-ENA antibodies, ACA, and anti-ß2 GPI antibodies yielded a sensitivity of 82.12% (80.41%-83.71%) and a specificity of 80.03% (76.77%-82.93%) for the diagnosis of SLE. Conclusion: The combination of age, sex, anti-ENA antibodies, ACA, and anti-ß2 GPI antibodies shows high diagnostic value for SLE and holds potential for clinical application as an auxiliary diagnostic tool for SLE.

Prevalence of a large panel of systemic autoantibodies in the Bavarian adult population.

Objective: Autoimmune diseases commonly feature the presence of specific humoral autoantibodies. However, the prevalence of a large panel of systemic autoantibodies has never been assessed in the general population. We, therefore, described the prevalence of about 50 humoral systemic autoantibodies in a sample of the general Bavarian adult population. Methods: Non-fasting venous serum samples from 331 participants were analyzed for 7 autoantibody screening tests (nuclear, cytoplasmic, and mitotic ANA, ANCA, cANCA and pANCA, anti-ENA autoantibodies) and 44 different monospecific humoral non-organ specific/systemic autoantibodies using indirect immunofluorescence tests, ELISAs, and line blots. In order to assess associations between sex, age, BMI, education level, smoking status and the presence of systemic autoantibodies, logistic regression analyses were conducted. Results: At least one screening test was positive in 29.9% of the participants, and 42.3% of the participants were seropositive for at least one monospecific autoantibody. The most frequently found monospecific autoantibodies were rheumatoid factor (35.6%), ß2-glycoprotein 1 IgM (4.8%), and cardiolipin IgG (1.8%). Only few associations between sex, age, BMI, education, smoking status and autoantibody frequencies were observed. Conclusion: Systemic autoantibodies are common in the general Bavarian population, and largely independent of sex, age, BMI, education, or smoking status. The study results may give orientation to clinicians about the occurrence of autoantibodies in the population, not (yet) associated with clinical symptoms.

Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Introduction: Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. Method: This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aß2GP1). Results: Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aß2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

A Case of Impending Central Retinal Vein Occlusion Associated With Antiphospholipid Antibody Syndrome Complicated by Paracentral Acute Intermediate Layer Maculopathy.

We report a case of impending central retinal vein occlusion (CRVO) due to antiphospholipid syndrome (APS) complicated by paracentral acute middle maculopathy (PAMM). A 42-year-old man with no medical history acutely presented with blurred vision in his right eye. The best-corrected visual acuity was 20/20 in the right eye, but the Goldman visual field test showed a dark spot over the superior nasal region of the right eye. Fundus examination showed dilated and tortuous retinal veins of the right eye with delayed filling of the inferior retinal veins on fluorescein angiography. Optical coherence tomography (OCT) showed a hyperreflective lesion confined to the inner nuclear layer (INL), consistent with PAMM. After several weeks, his symptoms improved, and the dilated retinal vein and the INL hyperreflexia on OCT were reduced. Multiple positive findings for anti-cardiolipin antibodies were confirmed; therefore, he was diagnosed with APS and treated with aspirin. If the impending CRVO is associated with visual impairment, the complication of PAMM should be considered. In the presence of retinal vasculopathy without atherosclerotic factors, APS should be considered.

Antiphospholipid Antibody Testing for Anti-cardiolipin and Anti-ß2 Glycoprotein I Antibodies Using Chemiluminescence-Based Panels.

Antiphospholipid (antibody) syndrome (APS) is a prothrombotic condition with increased risk for thrombosis and pregnancy-related morbidity. In addition to clinical criteria related to these risks, APS is characterized by the persistent presence of antiphospholipid antibodies (aPL), as detected in the laboratory using a potentially wide variety of assays. The three APS criteria-related assays are lupus anticoagulant (LA), as detected using clot-based assays, and the solid-phase assays of anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI), with immunoglobulin subclasses of IgG and/or IgM. These tests may also be used for the diagnosis of systemic lupus erythematosus (SLE). In particular, APS diagnosis/exclusion remains challenging for clinicians and laboratories because of the heterogeneity of clinical presentations in those being evaluated and the technical application and variety of the associated tests used in laboratories. Although LA testing is affected by a wide variety of anticoagulants, which are often given to APS patients to prevent any associated clinical morbidity, detection of solid-phase aPL is not influenced by these anticoagulants, and this thus represents a potential advantage to their application. On the other hand, various technical issues challenge accurate laboratory detection or exclusion of aPL. This report describes protocols for the assessment of solid-phase aPL, specifically aCL and aß2GPI of IgG and IgM class by means of a chemiluminescence-based assay panel. These protocols reflect tests able to be performed on the AcuStar instrument (Werfen/Instrumentation Laboratory). Certain regional approvals may also allow this testing to be performed on a BIO-FLASH instrument (Werfen/Instrumentation Laboratory).

The impact of antiphospholipid antibodies in Takayasu arteritis.

BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients.

In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.

Predictive value of anticardiolipin antibody and D-dimer combined with risk assessment profile for thromboembolism for deep vein thrombosis in elderly postoperative patients with intertrochanteric fracture of femur / 中国医师进修杂志

Objective:To investigate the predictive value of anticardiolipin antibody (ACA) and D-dimer (D-D) combined with risk assessment profile for thromboembolism (RAPT) for deep vein thrombosis (DVT) in elderly postoperative patients with intertrochanteric fracture of femur (IFF).Methods:The clinical data of 123 elderly patients with IFF in Suzhou Hospital Affiliated to Anhui Medical University from January 2019 to March 2022 were retrospectively analyzed. All patients underwent closed reduction intramedullary nail fixation. The patients were divided into DVT group (27 cases) and non-DVT group (96 cases) according to the presence or absence of DVT 7 d after surgery. Before surgery and 3, 5 d after operation, the ACA was detected by enzyme-linked immunosorbent assay, the D-D was detected by automatic coagulation analyzer, and RAPT was performed. The correlation among ACA, D-D and RAPT was analyzed by Spearman method. Multivariate Logistic regression was used to analyze the independent risk factors of DVT in elderly postoperative patients with IFF. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of ACA, D-D and RAPT in predicting DVT in elderly postoperative patients with IFF. The incidences of postoperative DVT in patients with different ACA, D-D and RAPT patients were compared.Results:There were no statistical difference in ACA, D-D and RAPT before operation between the two groups ( P>0.05); the ACA, D-D and RAPT 3 and 5 d after operation in DVT group were significantly higher than those in the non-DVT group, 3 d after operation: (12.44 ± 3.25) × 10 3 RU/L vs. (8.67 ± 2.81) × 10 3 RU/L, (7.29 ± 1.49) mg/L vs. (4.70 ± 1.23) mg/L and (9.79 ± 1.15) scores vs. (9.21 ± 1.32) scores; 5 d after operation: (10.28 ± 2.16) × 10 3 RU/L vs. (6.45 ± 2.04) × 10 3 RU/L, (5.49 ± 1.26) mg/L vs. (3.63 ± 1.05) mg/L and (9.57 ± 1.08) scores vs. (9.12 ± 0.70) scores, and there were statistical differences ( P<0.01 or <0.05). Since ACA, D-D and RAPT in the two groups all reached their peak 3 d after operation, this time point was selected for analysis. Three days after operation, Pearson correlation analysis result showed that ACA and D-D were positively correlated with RAPT ( r = 0.635 and 0.630, P<0.01), and ACA was positively correlated with D-D ( r = 0.657, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ACA and D-D combined RAPT 3 d after operation in predicting DVT in elderly postoperative patients with IFF was greater than that predicted by the 3 indexes alone (0.982 vs. 0.894, 0.870 and 0.868), the optimal cut-off values were 11.48 × 10 3 RU/L, 6.75 mg/L and 9 scores. According to the optimal cut-off value of ROC curve analysis at 3 d after operation, the patients were divided into ACA low expression (≤11.48 × 10 3 RU/L, 92 cases) and ACA high expression (>11.48 × 10 3 RU/L, 31 cases), D-D low expression (≤6.75 mg/L, 99 cases) and D-D high expression (>6.75 mg/L, 24 cases), low RAPT (≤9 scores, 93 cases) and high RAPT (>9 scores, 30 cases). The incidences of postoperative DVT in patients with ACA high expression, D-D high expression and high RAPT were significantly higher than those in patients with ACA low expression, D-D low expression and low RAPT: 43.39% (15/31) vs. 13.04% (12/92), 54.17% (13/24) vs. 14.14% (14/99) and 53.33% (16/30) vs. 11.83% (11/93), and there were statistical differences ( χ2 = 16.91, 18.06 and 22.81; P<0.01). After controlling for diabetes and other factors, multivariate Logistic regression analysis result showed that ACA, D-D and RAPT 3 d after operation were independent risk factors for DVT in elderly postoperative patients with IFF ( OR = 2.156, 2.276 and 6.106; 95% CI 1.356 to 3.429, 1.240 to 4.177 and 1.564 to 23.840; P<0.01). Conclusions:The ACA, D-D combined with RAPT can improve the predictive value of DVT in elderly postoperative patients with IFF, which has important reference significance for taking timely and effective intervention measures in early clinical stage.

Antiphospholipid antibodies in autoimmune thyroid diseases.

BACKGROUND: Antiphospholipid (aPL) antibodies have been reported in several autoimmune diseases. The aim of this study was to evaluate the frequency of aPL (anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI)) in patients with autoimmune thyroid diseases (AITD). METHODS: One hundred and ninety-five patients with AITD (139 Hashimoto's thyroiditis (HT) patients and 56 Graves' disease (GD) patients) and 90 healthy blood donors (HBD) were studied. IgG, IgA and IgM aCL and aß2GPI were determined by ELISA. RESULTS: One hundred fifty-four AITD patients were women and 41 were men. Fifty-six healthy subjects were women and 34 were men. The median age of patients and the control group was 45 and 38.5 years, respectively. The frequency of aPL was significantly higher in patients with AITD and in patients with HT than in HBD (33.3% vs 11.1%, p < 10-3 and 38.1% vs 11.1%, p < 10-3 ). The frequency of aPL in GD was significantly lower than in HT (21.4% vs 38.1%, p = 0.025). In patients with HT, aß2GPI (34.5%) was significantly more frequent than aCL (13.6%) (p < 10-3 ). The frequency of aß2GPI was significantly higher in patients with HT than in healthy population (34.5% vs 11.1%, p < 10-3 ). In HT patients, IgA isotype of aß2GPI was significantly more common than in HBD and in GD patients (27.3% vs 7.8%, p < 10-3 and 27.3% vs 12.5%, p = 0.02, respectively). CONCLUSION: aß2GPI and not aCL were frequent in AITD. IgA was the predominant isotype of aß2GPI. aß2GPI-IgA was more frequent in HT than in GD.

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI), but also non-criteria antibodies such as antibodies against ß2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-ß2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.

Anticardiolipin Antibodies Presenting With Acute Renal Infarction in a Healthy 26-Year-Old Female.

A 26-year-old female presented to the emergency department with right lower quadrant pain. This pain lasted a couple of days, worsened, and was associated with nausea but no vomiting. Upon presentation, physical examination showed tenderness to palpation in the right lower quadrant with bilateral purple non-blanching discolorations present on her toes and no costovertebral angle tenderness. Contrast-enhanced computed tomography (CT) showed acute right renal infarction. Thrombophilia workup was done, which showed elevated antinuclear antibodies and anticardiolipin antibodies. Elevated lactate dehydrogenase, c-reactive protein, and sedimentation rate were also found. No other inherited thrombophilia was discovered in lab work. Combined oral contraceptives were stopped, and the patient was started on enoxaparin followed by rivaroxaban upon discharge. The antiphospholipid syndrome commonly presents in young females as recurrent miscarriages, stroke, or deep venous thrombosis. Venous thrombosis is more common than arterial. Rare arterial thrombosis manifestations of this syndrome include coronary, retinal, mesenteric, and renal. This is a rare case of anticardiolipin antibodies presenting as an acute right renal infarction. This raises the question if clinicians should screen for inherited thrombophilia before prescribing oral contraceptives.

Cases of catastrophic anti-phospholipid syndrome in systemic lupus erythematosus: An experience.

Anti-phospholipid syndrome is an autoimmune disorder characterized by episodes of arterial and/or venous thrombosis and/or pregnancy morbidity in the presence of anti-phospholipid antibodies. Catastrophic anti-phospholipid syndrome is an accelerated form of the disease with rapid involvement of multiple organ systems often posing a diagnostic challenge. There is a paucity of literature on the myriad presentations of catastrophic anti-phospholipid syndrome owing to the orphan nature of the disease. We present three cases of catastrophic anti-phospholipid syndrome in patients with systemic lupus erythematosus that presented with episodes of thrombosis involving both arterial and venous systems and multisystem organ failure. Timely diagnoses were made based on a high index of suspicion and were managed with a combination of systemic glucocorticoids, cyclophosphamide, plasmapheresis, intravenous immunoglobulin and other supportive measures. However, despite providing the standard of care, we encountered a poor outcome in two of these patients, highlighting the high mortality associated with catastrophic anti-phospholipid syndrome.

Antiphospholipid antibodies in COVID-19-associated pneumonia patients in intensive care unit.

OBJECTIVES: Antiphospholipid antibodies (APAs) increase the risk of excessive blood clotting, but their role in COVID-19 remains unclear. We aimed to investigate the presence of conventional APAs used in the classification of antiphospholipid antibody syndrome in patients with severe lung infection with SARS-CoV-2 and to compare these results with non-COVID-19 critically ill patients. METHODS: Thirty-one COVID-19 patients (COVID group) and 28 non-COVID-19 critically ill patients (non-COVID group), were included in the study. Anti-cardiolipin (ACA) (IgG, IgM), anti-ß2-glycoprotein 1 (Anti-ß2GPI) (IgG, IgM, and IgA), and if the patient had not received any anti thrombotic agent before blood collection, lupus anticoagulant (LAC) tests were studied from the plasma of the patients. For testing ACA and Anti-ß2GPI, ELISA method was used, while fully automated coagulometer device was used for LAC test. RESULTS: APAs were positive in 25.81% in the COVID group (8/31) and 25% in the non-COVID group (7/28). LAC was the most common APA present in 23.08% of the COVID-19 group, who underwent measurement (6/26), while 3.57% of the non-COVID group was LAC positive (1/28) (p = .047). In the COVID group, ACA IgM, and IgG were positive in 6.45% and 0%, respectively (2/31 vs 0/31). In the non-COVID group, ACA IgM was not positive in any patient, while ACA IgG was positive in 7.14% (2/28). Anti-ß2GPI IgG and IgM tests were not positive in any patient in either the COVID or the non-COVID group. Anti-ß2GPI IgA were positive in 6.45% and 14.29%, respectively (2/31 vs 4/28). CONCLUSION: In this study, APAs were equally positive in critically ill patients among COVID-19 or non-COVID-19 patients. Only LAC was more observed in COVID-19 patients.